Division of Pediatric Ophthalmology, King Khaled Eye Specialist Hospital, Riyadh, Saudi Arabia.
Curr Opin Ophthalmol. 2011 Sep;22(5):347-55. doi: 10.1097/ICU.0b013e32834922d2.
To provide an overview of the genetics of the primary open-angle glaucomas with particular attention to congenital, infantile, and juvenile forms.
Mutations in CYP1B1, in addition to being the most common identifiable cause of autosomal recessive primary congenital/infantile glaucoma, can infrequently underlie juvenile and even primary adult-onset open-angle glaucoma, particularly in certain consanguineous populations. In 2009, patients diagnosed with congenital/infantile glaucoma were found to have recessive mutations in a second gene, LTBP2, with a phenotypic spectrum that includes primary megalocornea, spherophakia with ectopia lentis, and lens-related glaucoma. The most common identifiable cause of primary juvenile open-angle glaucoma across most populations remains heterozygous (autosomal dominant) MYOC mutation, underlying up to one-third of cases and possibly sometimes involved in earlier and later onset glaucomas Although primary adult-onset open-angle glaucoma usually does not follow simple Mendelian genetics and is etiologically complex, genome-wide association studies are uncovering genetic susceptibility factors. In some cases, primary adult-onset open-angle glaucoma can be caused by heterozygous mutation in MYOC, OPTN, or WDR36. In addition, in 2009, heterozygous NTF4 mutation was associated with the phenotype in a small percentage of patients from a German cohort.
Seemingly unaffected siblings of children with CYP1B1-related primary congenital/infantile glaucoma should undergo genetic testing because of variable expressivity for the phenotype; such testing should also be considered for other asymptomatic relatives, especially in consanguineous families. In western populations, dominant MYOC mutation remains a common cause of primary open-angle juvenile glaucoma and infrequently can be implicated in congenital/infantile or adult-onset forms; identified families should undergo genetic counseling. Primary adult-onset open-angle glaucoma rarely follows simple Mendelian genetics, but genomic studies in different populations are revealing potential genetic risk factors for the phenotype.
特别关注先天性、婴儿期和青少年型青光眼，概述原发性开角型青光眼的遗传学。
CYP1B1 的突变除了是常染色体隐性遗传的原发性先天性/婴儿型青光眼最常见的可识别病因之外，还可偶尔引起青少年型，甚至成人发病的原发性开角型青光眼，特别是在某些近亲人群中。2009 年，患有先天性/婴儿型青光眼的患者被发现存在第二个基因 LTBP2 的隐性突变，其表型谱包括原发性大角膜、晶状体异位性球形晶状体和晶状体相关青光眼。在大多数人群中，原发性青少年型开角型青光眼最常见的可识别病因仍然是杂合子（常染色体显性）MYOC 突变，占病例的三分之一左右，并且可能与早发和晚发青光眼有关。虽然原发性成人发病的开角型青光眼通常不符合简单的孟德尔遗传，并且病因复杂，但全基因组关联研究正在揭示遗传易感性因素。在某些情况下，原发性成人发病的开角型青光眼可能是由于 MYOC、OPTN 或 WDR36 的杂合突变引起。此外，2009 年，在一小部分来自德国队列的患者中，发现杂合 NTF4 突变与表型有关。
CYP1B1 相关原发性先天性/婴儿型青光眼患儿的似乎未受影响的同胞，由于表型的表现度可变，应进行基因检测；这种检测也应考虑用于其他无症状的亲属，特别是在近亲家庭中。在西方人群中，显性 MYOC 突变仍然是原发性开角型青少年型青光眼的常见病因，并且偶尔可与先天性/婴儿型或成人发病型有关；已识别的家族应进行遗传咨询。原发性成人发病的开角型青光眼很少遵循简单的孟德尔遗传，但不同人群的基因组研究正在揭示该表型的潜在遗传风险因素。
